Interest in developing a practical form of bandages or covers that are formed in situ on a wound by spraying a solution or dispersion of a polymer(s) in a liquid carrier dates back to the early 1970s, when for instance the preparation of a spray-on bandage was described in U.S. Pat. No. 3,577,516. In the latter the inventors outlined the requirements for a fully acceptable spray-on bandage to include the following:                (1) It protects the wound from air borne bacteria and dirt.        (2) It has moisture vapor permeability sufficient to prevent accumulation of aqueous fluid under the bandage.        (3) It must be non-toxic and non-irritating to the skin.        (4) It should not adhere to the wound area or permit infiltration by regenerating tissue.        (5) It should not cause a burning or stinging sensation when applied.        (6) It should not be water soluble or rendered tacky by contact with water to avoid dirt accumulation.        (7) It should be readily removable when desired.        
Those inventors also noted that prior art spray-on products suffer from a number of disadvantages with respect to the above criteria. Thus prior art materials having the desired moisture vapor permeability coupled with water resistance must be applied as a spray from alcohol or similar solvent solution which causes a strong burning sensation in the wound area. Hence, the objective of U.S. Pat. No. 3,577,516 was to develop a spray-on bandage having all seven of the above set forth desirable characteristics while avoiding the disadvantages of prior art spray-on bandages. More specifically U.S. Pat. No. 3,577,516 dealt primarily with a method of forming a powdery bandage in situ on skin having a wound therein which is readily removable therefrom after soaking, the improvement comprising the steps of (a) applying, as a powder, a hydrophilic water insoluble hydroxyl or lower alkoxy lower alkyl acrylate or methacrylate polymer or a copolymer of 20 to 70% of a lower acrylate or methacrylate and 80 to 30% of acrylamide, methacrylamide, N-lower alkyl acrylamide or methacrylamide, or N-vinylpyrrolidone as a powder and (b) applying, simultaneous or in succession, a high boiling liquid plasticizer or solvent therefor which does not cause a burning or stinging sensation when applied on the skin resulting from adherence of the powder to the wound area wet with the non-stinging plasticizer solvent thereby covering said wound wherein the polymer powder and plasticizer are sprayed from separate containers in succession, or wherein the polymer powder and plasticizer are simultaneously sprayed from separate chambers in a single container, or wherein the polymer powder and plasticizer are sprayed simultaneously from the same chamber in a single container, the plasticizer and polymer powder being kept separate by the propellant which prevents salvation and agglomeration of the polymer powder by the plasticizer, wherein the polymer is in finely divided form, substantially uncrosslinked and has a moisture vapor permeability of at least 200 grams/sq. meter/24 hours/mil and the application is accomplished by spraying as an aerosol with the aid of a propellant.
Extension of the in situ-forming film technology was described in U.S. Pat. No. 6,958,154 and dealt with a spray-on bandage and drug delivery system. This provided the so called patch-in-a-bottle technology in which a fluid composition, e.g., an aerosol spray, is applied onto a surface as a fluid, but then dries to form a covering element, such as a patch, having a tack-free outer surface covering an underlying adhesive that helps to adhere the patch to the substrate. The fluid compositions have a unique chemical formulation that allows such composite patches to form in situ. Specifically, the fluid compositions include a tacky component, such as an adhesive, and a film-forming, non-tacky component. The non-tacky and tacky components are selected to be immiscible with each other so that the components undergo phase separation as the fluid composition dries. Accordingly, U.S. Pat. No. 6,958,154 claimed a fluid composition suitable for in situ forming and adhering to a touch-dry, non-tacky covering element onto a surface, comprising:
(a) an effective amount of a tacky component such that the formed covering element adheres to the surface, wherein the tacky component comprises a pressure sensitive adhesive comprising a methacrylate polymer, further wherein the methacrylate polymer is a copolymer of monomers comprising about 40 to about 100 weight percent of an alkyl methacrylate and 0 to about 60 weight percent of a free radically 20 copolymerizable monomer;
(b) a film-forming, non-tacky component, wherein said film-forming; non-tacky component comprises at least one low surface energy, surface seeking moiety, wherein said film-forming, non-tacky component is incompatible with the tacky component, and wherein the film-forming, non-tacky component is present in an effective amount such that upon application it undergoes phase separation from the tacky component such that an outer surface of the in situ formed covering element is non-tacky when the covering element is touch dry; and
(c) a sufficient amount of at least one volatile solvent such that the fluid composition has a coatable viscosity allowing the fluid composition to be coated onto said surface.
In a series of disclosures (U.S. Pat. No. 4,987,893, U.S. Pat. No. 5,103,812, and U.S. patent application Ser. No. 11/465,237), conformable solvent-based bandage and coating materials were discussed by the inventors, specifically, combinations of alky siloxy siloxane-containing polymers admixed with liquid polydimethylsiloxanes are excellent non-stinging, non-irritating liquid coating material for forming films, which act as conformable bandages adhering to and protecting nails, skin and mucous membrane wounds from abrasion, contamination, and desiccation, while stopping pain from exposed nerve ends and allowing body fluid evaporation U.S. Pat. Nos. 4,987,893 and 5,103,812). In one primary claim (U.S. Pat. No. 4,987,893) the inventors described a liquid polymer-containing bandage material comprising 1 to 40 weight percent siloxane containing polymer, 59.9 to 98.9 weight percent volatile polydimethylsiloxane liquid, and 0.1 to 10 weight percent polar liquid; said bandage material being substantially non-stinging and film forming at room temperature to form an adherent conformable moisture vapor permeable bandage directly on a user. In a second major claim (U.S. Pat. No. 5,103,812), the inventors described a liquid polymer-containing coating material comprising from 1 to 40 weight percent siloxane containing polymer, 59.9 to 98.9 weight percent volatile polydimethylsiloxane, and 0.1 to 10 weight percent polar liquid; said coating material being substantially non-stinging and film forming at room temperature to form an adherent conformable moisture 35 vapor permeable coating directly on a user, wherein said siloxane-containing polymer is soluble in hexamethyldisiloxane and comprises a monomer component that is a silane derivative, a monomer component that when provided as a homopolymer would prepare a hard polymer, and a monomer component that, when provided as a homopolymer would prepare a soft polymer. In a subsequent disclosure, those inventors described liquid hemostatic coating materials that comprise a cyanoacrylate monomer and a solvent system comprising a volatile, non-reactive liquid that is non-stinging and non-irritating to a user. The material forms a coating or bandage in the form of a film that when applied and adhered to a surface or to the skin of a user inhibits the application surface from adhering to another surface (U.S. patent application Ser. No. 11/465,237). Specifically, the primary claims described a liquid coating material comprising about 0.1 to about 99.9 weight percent polymerizable cyanoacrylate monomer and about 0.1 to about 99.9 weight percent non-stinging, non-irritating, volatile, non-reactive liquid; said coating material being hemostatic on bloody, moist and non-moist surfaces to form an adherent, conformable polymer coating, which adherent, conformable coating does not adhere to a second surface, wherein the liquid coating comprises about 0.01 to about 99.5 percent by weight siloxysilane-containing polymer, about 0.1 to about 99.5% by weight polymerizable cyanoacrylate monomer and about 0.5 to about 99.9% by weight non-stinging, non-irritating, volatile hydrophobic liquid; said coating materials being film-forming on bloody, moist and non-moist surfaces to form an adherent, conformable, moisture vapor permeable, hemostatic, interpenetrating polymer coating, which coating does not adhere to a second surface, and wherein said polymerizable cyanoacrylate monomer component comprises alpha-cyanoacrylates.
Growing interest in exploring new biomedical applications of the absorbable polymer technology coupled with existing experience with in-situ forming non-absorbable film as discussed above directed the attention of Tipton et al. (U.S. Pat. Nos. 5,632,727 and 5,792,469) to the preparation of a biodegradable film dressing with or without additional therapeutic agents, an apparatus for spray delivery and a method for formation of the film dressing on a human or animal tissue. The film dressing is formed from a liquid composition of at least one biodegradable/bioerodible thermoplastic polymer in a pharmaceutically acceptable solvent. The spray apparatus includes a vessel containing the liquid composition with a dispensing means. The film is formed by dispensing, preferably by spraying, the liquid composition onto a tissue site and contacting the liquid composition with an aqueous-based fluid to coagulate or solidify the film onto the human or animal tissue. The biodegradable film can be used to protect and to promote healing of injured tissue and/or to deliver biologically active agents. The primary claims of these disclosures deal with a biodegradable microporous film dressing comprised of a skin and a core portion, the skin portion having pores with a smaller diameter than pores of the core portion; wherein the film dressing is formed by contacting a composition comprising a biodegradable thermoplastic polymer that is insoluble in aqueous or body fluids, and an organic solvent that is soluble in aqueous or body fluids, with an aqueous or body fluid whereupon the composition coagulates or solidifies to form the microporous film dressing, wherein the film dressing is formed by administering the composition onto tissue, and the core portion of the film dressing is orientated under the skin portion and in contact with the tissue, and further wherein the film dressing is formed by administering the composition onto a tissue and the skin portion of the film dressing is orientated under the core portion and in contact with the tissue. Meanwhile, the biodegradable thermoplastic polymer is selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polyethylene glycols, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(amino acids), poly (methyl vinyl ether) and copolymers, terpolymers, and combinations thereof. The solvent used in dissolving the polymers included N-methyl-2-pyrrolidone, 2-pyrrolidone, acetone, acetic acid, ethyl acetate, ethyl lactate, methyl acetate, methyl ethyl ketone, dimethylformamide, dimethylsulfoxide, dimethyl sulfone, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, propylene carbonate, N,N-diethyl-m-toluamide, and 1-dodecylazacycloheptan-2-one, and mixtures thereof. A second primary claim made by those inventors dealt with a liquid composition suitable for forming an in situ biodegradable film dressing on a human or animal tissue, comprising: a liquid formulation of a biodegradable thermoplastic polymer that is insoluble in aqueous or body fluids and an organic solvent that is soluble in aqueous or body fluids; wherein the composition comprises about 0.01-2 g polymer per mL solvent, and has a viscosity of about 45 0.1-2000 cps which effectively allows for aerosolization, and wherein the amount and molecular weight of said polymer is such that the composition is capable of coagulating or solidifying to form a film dressing upon contact with an aqueous or based fluid. Meanwhile, (1) the solvent is a liquid aerosol propellant that can be selected from the group consisting of trichloromonofluoromethane, dichlorodifluoromethane, dichloromonofluoromethane, 2-tetrafluoroethane, 1,1dichloro-1,2,2-tetrafluoroethane, 1-chloro-1,1difluoroethane, 1,1-difluoroethane, octofluorocyclobutane, propane, isobutane, N-butane, and mixtures thereof and (2) “biodegradable thermoplastic polymer is selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polyethylene glycols, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(amino acids), poly (methyl vinyl ether), and copolymers, terpolymers, and combinations thereof.
The use of a natural gum resin as a carrier for topical application of pharmacologically active agents was the subject of U.S. Pat. No. 6,899,897, which described a biological dressing for treatment of a dermatological disease comprised of a gum resin, a topically acceptable volatile solvent, and a pharmacologically active agent. The gum resin is present in a suitable amount that the composition, when the solvent evaporates, will dry to form a solid coating that sticks to the skin or mucosal membrane to which the composition is applied and maintain the pharmacologically active agent over a sustained period of time in contact with sites on the skin or mucosal membranes exhibiting symptoms of the disease. Methods are provided for treating symptoms of dermatological diseases with such a pharmacological composition. Biological dressings including tincture of benzoin and clotriconazole are shown to be efficacious for the long-term amelioration of symptoms of athlete's foot.
The primary claims of U.S. Pat. No. 6,899,897 dealt with a pharmacological composition comprising: (1) a gum resin, wherein said gum resin comprises benzoin; (1) at least one topically acceptable pharmacologically active agent other than said gum resin that is effective as a treatment for ameliorating symptoms of a disease of skin or a mucous membrane of a mammal wherein said pharmacologically active gent can remain in contact with said skin or said mucous membrane greater than 6 hours without toxic effects to said mammal; and (3) a topically acceptable volatile solvent for said gum resin and said pharmacologically active agent, wherein said topical acceptable volatile solvent is ethanol and the pharmacological active agent is the antimicrobial agent, clotriconazole.
All patents and patent applications noted in this specification are indicative of the level of skill of those skilled in the art to which the instant invention pertains. However, none of the prior art disclosures dealt with uniquely tailored in situ-formed bioactive tissue adherent films based, specifically, on absorbable crystallizable polymers in a non-irritating, highly volatile organic solvent to ensure optimum applicability, performance as a flexible tissue-adherant, conforming and stretchable protective cover that is also capable of a timely delivery of its drug payload and undergoing biodegradation thereafter. This and the availability of proprietary absorbable polymers in our laboratory that can be processed towards meeting the requirements of such film provided an incentive to pursue the study subject of the instant invention.